January 2022 – Cytogenetics and Laboratory Genetics and Genomics Case 2

The patient is a 34 year-old woman with a history of Diamond-Blackfan anemia. At age 25 she was diagnosed with myelodysplastic syndrome with 5q- syndrome. She began treatment with lenalidomide and continued for nine years with a complete response. Conventional chromosome analysis demonstrated a 5q deletion (Fig.1A). However, fluorescence in situ hybridization (FISH) was discordant and identified two intact copies of EGR1 (5q31) (Fig.1B). Chromosomal microarray was performed to further characterize the breakpoints of the 5q deletion (Fig.1C). 

Figure 1: A B and C

Why did the chromosome study not correlate with FISH?

  • The 5q interstitial deletion is telomeric to EGR1 (at 5q31).
  • The 5q interstitial deletion encompasses EGR1 and the FISH results do correlate.
  • It is best to investigate in the laboratory and inquire about a possible specimen mix-up.
  • Flow sorted cells for myeloid markers should have been used for FISH.

The correct answer is ...

The 5q interstitial deletion is telomeric to EGR1 (at 5q31).

Chromosomal microarray revealed that this bone marrow specimen contained two mosaic interstitial deletions on 5q involving loss of 5q22.1q22.2 and loss of 5q31.3q33.3 (including RPS14 and PDGFRB). Patients with atypical Diamond-Blackfan anemia can have somatically acquired 5q deletions involving RPS14 hapoloinsufficiency. Relying only on FISH using classic probes for the evaluation of MDS (including EGR1 at 5q31) will not represent the complete genomic profile of this malignancy. There is great value in the whole genome approach afforded by chromosome analysis in myeloid malignancies since they divide readily and not all 5q deletions are the same. 

Although it is never incorrect to investigate for a specimen mix-up, the integrated data do support that the FISH result is correct, because the array indicates the deletion is telomeric to EGR1

FISH testing is performed on direct specimen and therefore does not require sorted cells. 


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  2. Shaffer LG, Ballif BC, Schultz RA. The use of cytogenetic microarrays in myelodysplastic syndrome characterization. Methods Mol Biol. 2013;973:69-85. doi: 10.1007/978-1-62703-281-0_5. PMID: 23412784.
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Alaa Koleilat, Ph.D.

Resident, Laboratory Genetics and Genomics
Mayo Clinic

Patricia Greipp, D.O.      

Consultant, Hematopathology
Mayo Clinic
Assistant Professor of Laboratory Medicine
Mayo Clinic College of Medicine and Science

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This post was developed by our Education and Technical Publications Team.